Controlled-release Hydromorphone Research Articles

Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study

The incidence of infective endocarditis related to injection drug use is increasing. On the basis of clinical practice and epidemiological and in-vitro data, we postulated that exposure to controlled-release hydromorphone is associated with an increased risk of infective endocarditis among people who inject drugs. We used linked health administrative databases in Ontario, Canada, to assemble a retrospective cohort of adults (aged 18-55 years) who inject drugs for the period of April 1, 2006, to Sept 30, 2015. Cases of infective endocarditis among this cohort were identified using International Classification of Diseases 10 codes. We estimated exposure to hydromorphone and risk of infective endocarditis among this cohort in two ways. First, in a population-level analysis, we identified patients living in regions with high (≥25%) and low (≤15%) hydromorphone prescription rates and, after matching 1:1 on various baseline characteristics, compared their frequency of infective endocarditis. Second, in a patient-level analysis including only those with prescription drug data, we identified those who had filled prescriptions (ie, received the drug from the pharmacy) for controlled-release or immediate-release hydromorphone and, after matching 1:1 on various baseline characteristics, compared their frequency of infective endocarditis with that of patients who had filled prescriptions for other opioids. Between April 1, 2006, and Sept 30, 2015, 60 529 patients had evidence of injection drug use, 733 (1·2%, 95% CI 1·1-1·3) of whom had infective endocarditis. In the population-level analysis of 32 576 matched patients, we identified 254 (1·6%) admissions with infective endocarditis in regions with high hydromorphone use and 113 (0·7%) admissions in regions with low use (adjusted odds ratio [OR] 2·2, 95% CI 1·8-2·8, p<0·0001). In the patient-level analysis of 3884 matched patients, the frequency of infective endocarditis was higher among patients who filled prescriptions for hydromorphone than among those who filled prescriptions for non-hydromorphone opioids (2·8% [109 patients] vs 1·1% [41 patients]; adjusted OR 2·5, 95% CI 1·8-3·7, p<0·0001). This significant association was seen for controlled-release hydromorphone (3·9% [73 of 1895 patients] vs 1·1% [20 of 1895]; adjusted OR 3·3, 95% CI 2·1-5·6, p<0·0001), but not for immediate-release hydromorphone (1·8% [36 of 1989] vs 1·1% [21 of 1989]; 1·7, 0·9-3·6, p=0·072. Among people who inject drugs, the risk of infective endocarditis is significantly higher for those exposed to controlled-release hydromorphone than to other opioids. This association might be mediated by the controlled-release mechanism and should be the subject of further investigation. Ontario Ministry of Health and Long-Term Care, Academic Medical Organization of Southwestern Ontario, Schulich School of Medicine and Dentistry (Western University), and Lawson Health Research Institute.

Linking prescription opioids and infectious diseases

In Chicago, IL, USA, in the late 1970s, hospitalisations for infective endocarditis due to Pseudomonas aeruginosa began to increase among people who inject drugs. 1 Shekar R Rice TW Zierdt CH Kallick CA Outbreak of endocarditis caused by Pseudomonas aeruginosa serotype O11 among pentazocine and tripelennamine abusers in Chicago. J Infect Dis. 1985; 151: 203-208 Crossref PubMed Scopus (45) Google Scholar Once a rare occurrence, by 1980, P aeruginosa was the most common cause of endocarditis among people who inject drugs at Cook County Hospital (Chicago). It became clear, however, that P aeruginosa did not affect all individuals injecting drugs equally. It predominantly affected those injecting pentazocine, an opioid, and tripelennamine, an antihistamine (a combination known as T's and blues), which unlike heroin, were not boiled before injecting. 2 Botsford KB Weinstein RA Nathan CR Kabins SA Selective survival in pentazocine and tripelennamine of Pseudomonas aeruginosa serotype O11 from drug addicts. J Infect Dis. 1985; 151: 209-216 Crossref PubMed Scopus (31) Google Scholar This drug combination allowed P aeruginosa serotype O11 strains to survive, while inhibiting the growth of other P aeruginosa serotypes and Staphylococcus aureus, the latter being the main pathogen associated with infections in people using heroin. 1 Shekar R Rice TW Zierdt CH Kallick CA Outbreak of endocarditis caused by Pseudomonas aeruginosa serotype O11 among pentazocine and tripelennamine abusers in Chicago. J Infect Dis. 1985; 151: 203-208 Crossref PubMed Scopus (45) Google Scholar , 2 Botsford KB Weinstein RA Nathan CR Kabins SA Selective survival in pentazocine and tripelennamine of Pseudomonas aeruginosa serotype O11 from drug addicts. J Infect Dis. 1985; 151: 209-216 Crossref PubMed Scopus (31) Google Scholar In other words, the specific drugs and the way they were injected modulated the risk for a particular infection, with T's and blues serving as a selective medium for P aeruginosa O11. Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort studyAmong people who inject drugs, the risk of infective endocarditis is significantly higher for those exposed to controlled-release hydromorphone than to other opioids. This association might be mediated by the controlled-release mechanism and should be the subject of further investigation. Full-Text PDF

A Multifaceted Approach to Improve the Availability and Accessibility of Opioids for the Treatment of Cancer Pain in Serbia: Results From the International Pain Policy Fellowship (2006–2012) and Recommendations for Action

Cancer is the second leading cause of death in Serbia, and at least 14,000–16,000 patients experience moderate-to-severe cancer pain every year. Cancer pain relief has been impeded by inadequate availability of opioid analgesics and barriers to their accessibility. In 2006, a Serbian oncologist was selected as an International Pain Policy Fellow. The fellow identified barriers to opioid availability in Serbia and implemented an action plan to address the unavailability of oral morphine, attitudinal and knowledge barriers about opioids, and barriers in the national opioid control policy, in collaboration with the government, local partners, and international experts, including those from the World Health Organization. Collaborative efforts resulted in availability of immediate-release oral morphine, registration of controlled-release hydromorphone, and reimbursement of oral methadone for cancer pain; numerous educational activities aimed at changing inadequate knowledge and negative attitudes toward opioids; recognition of opioids as essential medicines for palliative care in a new National Palliative Care Strategy; and recognition of the medical use of opioids as psychoactive-controlled substances for the relief of pain included in a new national law on psychoactive-controlled substances, and the development of recommendations for updating regulations on prescribing and dispensing opioids. An increase in opioid consumption at the institutional and national levels also was observed. This article outlines a multifaceted approach to improving access to strong opioids for cancer pain management and palliative care in a middle-income country and offers a potential road map to success.

Quarta idade e velhice extrema: substituição da polifarmácia por um comprimido de hidromorfona de liberação controlada para o controle da dor crônica

JUSTIFICATIVA E OBJETIVOS: Cerca de 4,5 milhões de pessoas terão idade superior a 80 anos até 2020. Frequentemente, esta população necessita de polifarmácia para o controle da dor. O objetivo deste estudo foi avaliar a eficácia, custo e segurança da administração única, diária de hidromorfona de liberação controlada em pacientes com idade > 80 anos. MÉTODO: Oito pacientes (82 a 89 anos, quarta idade), e dois pacientes (93 e 99 anos, velhice extrema) foram avaliados. Todos utilizavam opioides, antidepressivos, anti-inflamatórios não esteroides, paracetamol e anticonvulsivantes para o controle da dor. Todos os fármacos com finalidade analgésica foram substituídos por um comprimido diário de 8 mg de hidromorfona de liberação controlada (OROS). Dor e efeitos adversos foram avaliados. RESULTADOS: O número de comprimidos diários para controle da dor diminuiu de 6-7 para um de hidromorfona. Houve diminuição da sensação de mal estar gástrico matinal, secundária à ingestão de grande número de comprimidos. Não foram relatadas náusea ou indisposição. Não foi relatada sonolência diária, sendo que os pacientes referiram melhor padrão de sono. CONCLUSÃO: A substituição da polifarmácia por um comprimido diário de hidromorfona melhorou o padrão analgésico, com baixa incidência de efeitos adversos em pacientes idosos, portadores de dor crônica, podendo ser considerada como uma boa alternativa para o controle da dor e a melhora da qualidade de vida desta população.

Retardiertes Hydromorphon bei viszeralen, somatischen und neuropathischen Schmerzen

The aim of this multicentre, longitudinal investigation was to document the efficacy and tolerability profiles of controlled release hydromorphone in patients with heavy visceral, somatic or neuropathic pain under practical conditions. To this end, a prospective observational study was conducted in 57 centres in Switzerland, on a total of 196 patients. After an average of 43 days of treatment with controlled release hydromorphone, the intensity of momentary pain dropped by 46.5% and that of maximum pain dropped by 41.3%, with the efficacy of the treatment being most pronounced with visceral and somatic pain. At the same time, the prevalence of sleep disorders as a result of pain decreased from initially 86.7% to 21.0%. Controlled release hydromorphone was excellently tolerated in this group of elderly (average age 70.6 years), multimorbid pain patients receiving various medical treatments (average of 2.4 drugs in addition to pain medication), even in the voluntary long-term extension study of up to 96 days. No medical interactions were reported. Six and thirteen weeks after introducing the treatment, 89.8% and 85.2%, respectively, were still taking controlled release hydromorphone. Controlled release hydromorphone is a recommendable option for practical treatment of heavy and extremely heavy pain of various genesis.

Gastrointestinal symptoms under opioid therapy: A prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine

Introduction The purpose of this trial was to evaluate the effect of long-term treatment with oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine on nausea, emesis and constipation. Patients and methods Randomly selected outpatients with cancer pain receiving one of the study medications were enrolled in a prospective, open-labeled, controlled trial ( n = 174). Mobility, pain, and gastrointestinal symptoms were assessed directly and per selected item on the ECOG (Eastern Cancer Oncology Group), EORTC (European Organisation for Research and Treatment of Cancer) questionnaires, NRS (Numerical Rating Scales), and analyzed statistically. Results Demographic and medical data were comparable in all groups. Only 15% of patients suffered from constipation. 59% took the prescribed laxatives. The incidence of stool free periods >72 h was significantly higher with transdermal opioids (transdermal fentanyl: 22%; transdermal buprenorphine: 21%; oral hydromorphone: 2%; p = 0.003). 21% of patients revealed nausea and emesis. The mean NRS for nausea (transdermal fentanyl:1.3; transdermal buprenorphine: 1.2; oral hydromorphone: 1.5; p = 0.6), the consumption of antiemetics (transdermal fentanyl: 42%; transdermal buprenorphine: 33%; oral hydromorphone: 36%; p = 0.6) and laxatives (transdermal fentanyl:53%; transdermal buprenorphine:66%; oral hydromorphone: 61%; p = 0.2) did not differ significantly, in contrast to the score for emesis (transdermal fentanyl: 16%; transdermal buprenorphine:13%; oral hydromorphone: 33%; p = 0.02). Morphine equivalent opioid doses differed (mg/d transdermal fentanyl: 183; transdermal buprenorphine: 89; oral hydromorphone: 143; p = 0.001), because of obvious tolerance varying after long-term treatment. Conclusions Gastrointestinal symptoms of cancer pain patients undergoing an opioid therapy are related to multifactorial causes. Transdermal opioids showed no benefit over oral controlled-release hydromorphone with regard to gastrointestinal symptoms. The conversion ratios for transdermal fentanyl, transdermal buprenorphine, and oral hydromorphone did not accord to the literature, because of differing occurrences of opioid tolerance after long-term therapy.

Hydromorphone in elderly patients with polypathia and with severe pain

There continue to exist serious deficiencies in the analgesic therapy of elderly patients and patients with polypathia and severe pain. Orally administered controlled-release hydromorphone (see Note 1) appears to be particularly suitable for this patient group due to its pharmacological and metabolic benefits. The aim of the present prospective, multicentre study was to analyse the effects of hydromorphone therapy on quality of analgesia and potential side effects. Patients and methods. 567 elderly patients with severe, predominantly tumour-related or musculoskeletal pain were included in this study. The majority of these patients had received prior analgesic therapy. The following parameters were measured before initiating treatment with orally administered controlled-release hydromorphone and at three further assessments during the therapy: the daily dose required, intensity of pain (measured on the Numeric Rating Scale: 0 = no pain to 10 = worst pain imaginable); typical opioid-related side effects such as tiredness, nausea, vomiting, constipation, pruritus; and severe adverse events, e.g. hospitalisation due to tumour therapy, dyspnoea, urinary retention. Pain-related interferences were assessed in seven spheres of life: general activity, mobility, social relationships, enjoyment of life, mood, resilience, sleep. Furthermore, the quality of life was assessed by means of the 'Brief Pain Inventory' developed by Cleeland as well as in diaries. A differentiated final assessment with regard to efficacy, tolerability and compliance was performed by the physician on completion of the study using a 5-point scale. Results. Within three weeks of therapy with controlled-release hydromorphone, intensity of pain was reduced by 65.7% on average, from 7.0 at the beginning to 2.4 at the final assessment. Typical opioid-related side effects frequently present at the beginning of the study decreased during therapy with hydromorphone by 88.6% on average. Therapy resulted in a reduction in pain-related interference by 50.7% and thus in a marked improvement in quality of life. In the final assessment by the physician both, efficacy and tolerability, as well as compliance were rated as 'very good' or 'good' in more than 80% of patients. Conclusion. The advantages of controlled-release hydromorphone offer an appropriate analgesic therapy even for elderly patients and patients with polypathia in the clinical and outpatient setting. Hydromorphone was well tolerated and effective in the treatment of severe pain. Quality of life improves substantially as a result of a marked decrease in opioid-related side effects and interferences in daily life. Prior to inclusion in this study, only a few patients with severe pain were treated with WHO-level III opioids indicating that blatant inadequacies in tumour pain therapy continue to exist.

Pain therapy in multiple myeloma — clinical experience from an observational study

Abstract Aim: The aim of the present study was the documentation and evaluation of analgesic therapy in patients with multiple myeloma. Method: As part of a chemotherapy optimisation study, the patients' pain therapy was documented. The severity of pain was recorded using a visual analogue scale (VAS) from 0 (neither pain nor impairment) to 10 (greatest imaginable pain, and very severe impairment). Follow-up examinations took place after 3 days, 1 month and 3 months. Results: 123 patients (60.9%) of 202 patients with multiple myeloma stage III, were treated with analgesics because of severe pain. The average duration of documentation was 11.6 months. One hundred patients received analgesics orally or transdermally, and 32 of these patients received oral controlled-release hydromorphone (Palladon® retard). The remaining patients received analgesic treatment with bisphosponates i.v. and non-medication measures. Four patients (n = 19) were treated with a transdermal system and 8 patients who received a diffe...

Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine.

An uncontrolled retrospective study was conducted looking at the use of oral controlled-release hydromorphone in palliative care patients. Over a 2-year period 55 patients were switched to hydromorphone therapy, and the efficacy and outcomes were assessed. Urea and electrolyte measurements were also recorded at the time of opioid switch and renal impairment defined as urea > 10.5 mmol/l and/or creatinine > or = 101 mmol/l. This group of 29 patients with abnormal urea and/or creatinine (Group 1) was compared with the remaining 26 patients (Group 2) who had normal urea and creatinine. The major reasons for change to hydromorphone were side-effects (cognitive/drowsiness/nausea) on previous therapy. Following a switch to hydromorphone these side-effects improved in over 80% of patients (n = 55). Comparison between Group 1 and 2 demonstrated a significant difference in renal function but no significant differences in reasons for change, dose of opioids or response to change (over 80% improvement following opioid switch). We conclude that hydromorphone is a flexible second-line alternative to morphine that is particularly useful when intolerable side-effects are experienced with other opioids. In renal impairment (including two patients with end-stage renal failure) we found hydromorphone to be safe and effective. Further clinical and pharmacokinetic studies are required.

Hydromorphone--review of pharmacological properties and therapeutic efficacy with special regard to a controlled release preparation

Hydromorphone is a micro receptor agonist opioid. According to WHO recommendations, hydromorphone is to be classified in step III of pain therapy. An oral formulation with a prolonged duration of action of 12 hours has been evaluated only recently. The controlled release capsule is especially suited for the regular twice a day administration in cases of severe and persistent pain. The oral formulation of hydromorphone increases the number of opioid analgesics available for pain therapy in step III. Hydromorphone is recommended when morphine fails to produce sufficient pain relief (despite increase of doses) or causes intolerable side effects (despite treatment of symptoms). In principle, no differences in efficacy of morphine and hydromorphone are to be expected. However, clinical experience shows that changing one opioid analgesic to another one can improve the treatment of patients so that hydromorphone may replace another opioid analgesic to which a patient fails to respond well or develops side effects. The dose of hydromorphone equivalent to 2 times 30 mg controlled release morphine is about 2 times 4 mg. The values for the absorption, bioavailability and maximum plasma concentration after the administration of controlled release hydromorphone every 12 hours -of three times the dose- are equivalent to those of an immediate release tablet given every 4 hours. In several open label and controlled studies, hydromorphone proved to be of good efficacy in the treatment of acute and persistent pain, especially in patients with severe cancer pain. With regard to the incidence of side effects, no significant differences between morphine and hydromorphone could be established. In general, the side effects of hydromorphone are typical for opioid analgesics. In conclusion, controlled release hydromorphone seems to be well suited for the control of severe chronic pain when given twice daily.

Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain

The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain. In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded. Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone. Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management.